Human papillomavirus (HPVs) is the most common causing agents for cervical cancer. Although the introduction of vaccination is reducing its prevalence, there is still no reliable treatment for HPV infections. Understanding the life cycle of HPV, especially the regulation of the viral E6 and E7 gene expression, is crucial because its dysregulation is associated with tumor development. This study aims to investigate the complex mechanism of HPV16 E6/E7 mRNA splicing with a focus on the regulatory role of RNA binding proteins, particularly members of the serine and arginine (SR) rich protein family. Our results indicate that SRSF2 enhances HPV16 SD226-SA409 mRNA splicing is of significance since the SD226-SA409-spliced mRNA is coding for the HPV16 oncogenes, thus 226-409 splicing is a  potential therapeutic target.